The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
CDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers
Open accessAbstract
Deregulation of the cell cycle machinery is a hallmark of cancer. While CDK4/6 inhibitors are FDA approved (palbociclib) for treating advanced estrogen receptor-positive breast cancer, two major clinical challenges remain: (i) adverse events leading to therapy discontinuation and (ii) lack of reliable biomarkers. Here we report that breast cancer cells activate autophagy in response to palbociclib, and that the combination of autophagy and CDK4/6 inhibitors induces irreversible growth inhibition and senescence in vitro, and diminishes growth of cell line and patient-derived xenograft tumours in vivo. Furthermore, intact G1/S transition (Rb-positive and low-molecular-weight isoform of cyclin E (cytoplasmic)-negative) is a reliable prognostic biomarker in ER positive breast cancer patients, and predictive of preclinical sensitivity to this drug combination. Inhibition of CDK4/6 and autophagy is also synergistic in other solid cancers with an intact G1/S checkpoint, providing a novel and promising biomarker-driven combination therapeutic strategy to treat breast and other solid tumours.
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Cited by
Onorati, A. V., Dyczynski, M., Ojha, R., & Amaravadi, R. K. (2018) · Cancer · doi:10.1002/cncr.31335 · Cited by 837
Self-citationSenescent Cells in Cancer Therapy: Friends or Foes?
Wang, B., Kohli, J., & Demaria, M. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.05.004 · Cited by 508
Immunomodulation by anticancer cell cycle inhibitors
Petroni, G., Formenti, S. C., Chen-Kiang, S., & Galluzzi, L. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0300-y · Cited by 163
Combination Therapies with CDK4/6 Inhibitors to Treat KRAS- Mutant Pancreatic Cancer
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Senescence as a therapeutically relevant response to CDK4/6 inhibitors
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Metadata
- Authors
- Vijayaraghavan, S., Karakas, C., Doostan, I., Chen, X., Bui, T., Yi, M., Raghavendra, A. S., Zhao, Y., Bashour, S. I., Ibrahim, N. K., Karuturi, M., Wang, J., Winkler, J. D., Amaravadi, R. K., Hunt, K. K., Tripathy, D., & Keyomarsi, K.
- Venue
- Nature Communications
- Published
- 2017-06-27
- Volume
- 8
- Issue
- 1
- Pages
- 15916-15916
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2678824027
- Cited by
- 292
- References
- 69
- FWCI
- 22.48
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: CDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers. https://app.cochat.ai/papers/10.1038/ncomms15916
- The paper
- Vijayaraghavan, S., Karakas, C., Doostan, I., Chen, X., Bui, T., Yi, M., Raghavendra, A. S., Zhao, Y., Bashour, S. I., Ibrahim, N. K., Karuturi, M., Wang, J., Winkler, J. D., Amaravadi, R. K., Hunt, K. K., Tripathy, D., & Keyomarsi, K. (2017). CDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers. Nature Communications. https://doi.org/10.1038/ncomms15916
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
